Related Experiment Video

Updated: Apr 21, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Progesterone receptor-NFκB complex formation is required for progesterone-induced NFκB nuclear translocation and

Sung-Po Hsu¹, Ho-Ching Yang, Chun-Ting Kuo

¹Department of Physiology (S.-P.H., W.-S.L.), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Physiology (H.-C.Y.), College of Medicine, National Taiwan University, Taipei 100, Taiwan; Graduate Institute of Medical Sciences (C.-T.K., H.-C.W., L.-C.C., Y.-N.H., W.-S.L.), College of Medicine, Taipei Medical University, Taipei 110, Taiwan; and Cancer Research Center (W.-S.L.), Taipei Medical University Hospital, Taipei 110, Taiwan.

|October 30, 2014

Abstract:

We previously demonstrated that progesterone (P4) up-regulates p53 expression in human umbilical venous endothelial cells (HUVECs) through P4 receptor (PR) activation of extranuclear signaling pathways. However, the involvement of nuclear PR in P4-increased p53 expression is still unclear. Here, the molecular mechanism underlying PR-regulated p53 expression in HUVECs was investigated. Treatment with P4 increased nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α phosphorylation (IκBα and nuclear factor-κB (NFκB) nuclear translocation. Interestingly, P4 also increased PR-A, but not PR-B, nuclear translocation in HUVECs. Immunoprecipitation assay illustrated that P4 increased the formation of PR-A-NFκB complex in both the cytosol and the nucleus of HUVEC. Chromatin immunoprecipitation assay showed an interaction between PR and the NFκB binding motif on the p53 promoter. Ablation of the NFκB binding motif in the p53 promoter completely abolished P4-increased p53 promoter activity. In the absence of P4, overexpression of NFκB did not increase NFκB nuclear translocation. In contrast, treatment of NFκB-overexpressing HUVECs with P4 for only 4 hours, which is much shorter than the time (21.5 h) required for P4-induced IκBα phosphorylation, increased NFκB nuclear translocation. Blockade of PR activity abolished this effect. Taken together, these results uncover a novel role of PR for P4-induced NFκB nuclear translocation and suggest that PR-A-NFκB complex formation is required for NFκB nuclear translocation and binding onto the p53 promoter in HUVECs. Our data indicate that both nuclear and extranuclear signaling pathways of PR are involved in P4-regulated p53 expression in HUVECs.

More Related Videos

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Related Concept Videos

NF-κB-dependent Signaling Pathway

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...

Co-activators and Co-repressors

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...

Regulation of Nuclear Protein Sorting

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

NF-kB-dependent Signaling Pathway

NF-kB-dependent Signaling Pathway

Negative Regulator Molecules

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.

Articles linked to this work by shared authors, journal, and citation graph.

Engineered α9-nAChR-targeting antibodies attenuate nicotine-enhanced triple-negative breast cancer progression and exhibit favorable short-term tolerability in cynomolgus macaques.

Biomaterials·2026

Systemic Interventions Targeting Epidermal Barrier Function: Translational Insights from Oral Probiotics.

Skin pharmacology and physiology·2026

Forty-seven percent of pregnancies have stigmatizing language in their clinical notes in an electronic health record cohort.

medRxiv : the preprint server for health sciences·2026

From Zero-Shot to Bedside: A Practical Playbook for Adapting Open-Source Large Language Models to Clinical Symptom Extraction.

Proceedings of machine learning research·2026

Erratum: StAR-related lipid transfer domain protein 3 (STARD3) regulates HER2 and promotes HER2-positive breast cancer progression through interaction with HSP90 and SRC signaling.

American journal of cancer research·2026

Doublecortin-like kinase 1 promotes fibroblast activation and fibrotic progression through Smad3 binding in idiopathic pulmonary fibrosis.

Journal of biomedical science·2026

See all related articles